CYTOKINE REGULATION OF LACTATE DEHYDROGENASE-ELEVATING VIRUS - INHIBITION OF VIRAL REPLICATION BY INTERFERON-GAMMA

The mechanisms which regulate the replication of lactate dehydrogenase -elevating virus (LDV), a persistent murine model virus which infects macrophages, are unclear. For this study, the effects of murine recomb inant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TN F-alpha) on LDV replication were examined. LDV permissiveness was redu ced in macrophages obtained from uninfected mice treated with IFN-gamm a prior to cell harvest and in vitro LDV infection. Virus inhibition b y IFN-gamma was also observed when neonatal LDV-infected mice were inj ected with this cytokine prior to macrophage harvest and analysis of L DV replication-positive cells. Persistently LDV-infected mice demonstr ated an increase in viremia levels following treatment with TNF-alpha. Neither IFN-gamma nor TNF-alpha had any direct in vitro effect on LDV replication in cultured macrophages, suggesting that the actions of t hese cytokines required secondary or accessory in vivo events. These r esults provide evidence for cytokine-mediated regulation of LDV infect ion and support a role for the immune system in the LDV-host relations hip.